AMPA/kainate and Group-I Metabotropic Receptor Antagonists Infused into Different Brain Areas Impair Memory Formation of Inhibitory Avoidance in Rats

Several lines of evidence suggest that glutamate receptors are involved in memory processing. To examine the role of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors on memory consolidation, rats were bilaterally implanted with cannulae aimed at the CA1 region of the dorsal hippocampus (CA1), entorhinal cortex (ENTO), posterior parietal cortex (PPC) or the basolateral nucleus of the amygdala (BLA), and trained in a one-trial step-down inhibitory avoidance task. At different times after training, the alpha-amino 3-hydroxy-5 methyl 4-isoxazole propionate (AMPA) receptor blocker, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (1.0 microg/side), or the metabotropic type-I receptor antagonist, 2-amino-3-phosphonopropionic acid (AP3) (1.0 microg/side), were infused into the above-mentioned structures. CNQX produced retrograde amnesia when infused into BLA or CA1 0, 30, 90 or 180 min post-training but not at later times. AP3 blocked memory consolidation when administered into CA1 0, 30 or 180 min post-training, while in BLA, it was amnestic only when given 0 or 30 min after the training session. CNQX and AP3 had no effect on memory when administered into ENTO or PPC at any time. Our data suggest that the consolidation of the avoidance memory requires intact non-NMDA receptor function in the hippocampus and the basolateral nucleus of the amygdala, but not necessarily in the entorhinal and parietal cortex, for long periods after training.